Interleukin 37 Suppresses M1 Macrophage Polarization Through Inhibition of the Notch1 and Nuclear Factor Kappa B Pathways
Interleukin 37 Suppresses M1 Macrophage Polarization Through Inhibition of the Notch1 and Nuclear Factor Kappa B Pathways
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白细胞介素 37 通过抑制 Notch1 和核因子 Kappa B 通路来抑制 M1 巨噬细胞极化
DOI：
10.3389/fcell.2020.00056
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发表时间：
2020-02
影响因子：
5.5
通讯作者：
Qingchun Zeng
中科院分区：
文献类型：
--
作者：
Peitao Zhou;Qianqin Li;Shuwen Su;Wenhui Dong;Suyu Zong;Qiong Ma;Xi Yang;Daming Zuo;Shaoyi Zheng;Xianzhong Meng;Dingli Xu;Qingchun Zeng
巨噬细胞介导的慢性炎症在心血管疾病中起重要作用，包括加速钙化性主动脉瓣疾病（CAVD）的发展。M1和M2巨噬细胞极化失衡可以改变炎症反应的强度。重组人白细胞介素37（IL-37）可能参与调节免疫细胞功能以减轻炎症。本研究旨在鉴定IL-37特异性调节M1极化并研究其潜在机制。与正常主动脉瓣相比，钙化主动脉瓣中M1巨噬细胞聚集较多，IL-37表达较少，提示IL-37与M1极化呈负相关。THP-1细胞经佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）诱导分化为静息巨噬细胞，经脂多糖（LPS）和干扰素γ（IFN-γ）诱导分化为M1巨噬细胞。在体外，重组人IL-37减弱诱导型一氧化氮合酶（iNOS），CD 11 c，IL-6和单核细胞趋化蛋白1（MCP-1）在M1的表达，但增加的表达CD 206和IL-10在M2。M1极化的抑制与核因子κ B（NF-κB）和Notch 1信号通路的激活抑制有关。这些结果表明，IL-37通过抑制Notch 1和核因子κ B途径抑制巨噬细胞极化为M1型。总之，IL-37可能是通过调节M1极化及其协调的炎症来治疗进行性CAVD的潜在候选药物。
Macrophage-orchestrated chronic inflammation plays an important role in cardiovascular disease, including accelerating the development of calcific aortic valve disease (CAVD). M1 and M2 macrophage polarization imbalances can alter intensity of inflammatory responses. Recombinant human interleukin 37 (IL-37) could be involved in regulating immune cell function to attenuate inflammation. This study aimed to identify IL-37 specifically modulates M1 polarization and investigate the underlying mechanism. Compared with normal valves, there are more M1 macrophages accumulation and less IL-37 expression in calcific aortic valves, which may indicate a negative relationship between IL-37 and M1 polarization. THP-1 cells could differentiate into resting macrophages with phorbol-12-myristate-13-acetate (PMA) and then polarize into M1 macrophages following treatment with lipopolysaccharide (LPS) and interferon gamma (IFN-γ). In vitro, recombinant human IL-37 attenuated the expression of inducible nitric oxide synthase (iNOS), CD11c, IL-6 and monocyte chemoattractant protein 1 (MCP-1) in M1 but augmented the expression of CD206 and IL-10 in M2. The suppression of M1 polarization was associated with the inhibition of the activation of the nuclear factor kappa B (NF-κB) and Notch1 signaling pathways. These results demonstrated that IL-37 inhibits the macrophages polarizing into M1 type via the inhibition of the Notch1 and nuclear factor kappa B pathways. In summary, IL-37 could be a potential therapeutic candidate for progressive CAVD by modulating M1 polarization and its orchestrated inflammation.
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DOI：
10.1161/atvbaha.112.300116
发表时间：
2012-11
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Song R;Zeng Q;Ao L;Yu JA;Cleveland JC;Zhao KS;Fullerton DA;Meng X
通讯作者：
Meng X
Interleukin-1家族：回到未来。
影响因子：
32.4
作者：
Garlanda C;Dinarello CA;Mantovani A
通讯作者：
Mantovani A
DOI：
10.1161/atvbaha.107.154989
发表时间：
2008-01-01
影响因子：
8.7
作者：
Mohty, Dania;Pibarot, Philippe;Mathieu, Patrick
通讯作者：
Mathieu, Patrick
影响因子：
15.9
作者：
Adamson, Samantha E.;Griffiths, Rachael;Leitinger, Norbert
通讯作者：
Leitinger, Norbert
DOI：
10.1007/978-94-024-0921-5_2
发表时间：
2016-01-01
期刊：
REGULATION OF CYTOKINE GENE EXPRESSION IN IMMUNITY AND DISEASES
影响因子：
--
作者：
Yazdi, Amir S.;Ghoreschi, Kamran
通讯作者：
Ghoreschi, Kamran